Neuroprotective Role of Albizia lebbeck Leaves Against Cisplatin-Induced Neuropathic Pain via Modulating NF-κB...

This study aimed to evaluate the neuroprotective potential of Albizia lebbeck leaves extract (ALLE) against chemotherapy-induced peripheral neuropathy (CIPN). Ethanol-extracted ALLEs were analysed using GC-MS to identify major phytoconstituents. Thunbergol, lupenone and squalene were identified as key bioactive compounds. ADMET profiling using SwissADME and pkCSM revealed favourable pharmacokinetic and safety profiles, particularly for thunbergol and lupenone. Network pharmacology analysis indicated potential modulation of the NF-κB signalling pathway, a key mediator in neuroinflammation. Molecular docking and dynamic simulations confirmed strong binding affinity and stability of active compounds with target proteins. An in vivo CIPN model was established in mice to validate these findings. Animals were administered ALLEs (200 and 400 mg/kg, po) and compared with a standard group receiving gabapentin (100 mg/kg, po). Behavioural assessments (tail flick, cold allodynia and hot plate tests) significantly reduced neuropathic pain symptoms. Biochemical assays showed decreased levels of inflammatory cytokines (TNF-α, IL-1β and IL-6), and histopathological analysis of sciatic nerves revealed reduced inflammation and preserved axonal integrity. In conclusion, ALLEs exhibits significant neuroprotective effects against cisplatin-induced neuropathic pain, primarily through modulation of the NF-κB pathway. These findings support further exploration of A. lebbeck as a natural therapeutic candidate for CIPN management.